Association between grit and insomnia: A population-based study.

BACKGROUND: This study aimed to investigate the association of the grit scale, a personality trait characterized by perseverance and passion, with both the presence and the severity of insomnia in the Korean adult population. METHODS: A nationwide population-based cross-sectional survey was conducted through face-to-face interviews using structured questionnaires between September and December 2018 in Korea. Grit was assessed by using the 8-item Short Grit Scale. Participants were categorized into insomnia and non-insomnia groups based on a threshold of 10 on the Insomnia Severity Index (ISI). The association between girt and insomnia was analyzed using multiple linear regression and multivariable logistic regression, controlling for sociodemographic factors, lifestyles, and comorbidities. RESULTS: A total of 2453 participants (49.9 % male; aged 19-92 years) were enrolled in the study. Individual grit scores ranged from 1.75 to 5.00 points (mean [SD], 3.27 [0.42]), and insomnia was present in 16.5 % of the population. The insomnia group exhibited lower grit score compared to the non-insomnia group (3.11 [0.40] vs. 3.30 [0.42], p < 0.001, Cohen's d = 0.46). Grit was negatively associated with ISI scores (ß = -0.15, 95 % CI = -0.19, -0.11, p < 0.001) and with having insomnia (OR 0.40, 95 % CI = 0.30, 0.55, p < 0.001), after controlling for covariates. CONCLUSIONS: Individuals with higher grit were less likely to have insomnia. Clinicians should consider personality traits, such as grit, in the evaluation and the management of insomnia.

Cardiovascular Implications of Sleep Disorders Beyond Sleep Apnea.

Purpose of Review: Sleep is crucial for human health and life. There is still limited attention to the association between sleep disorders beyond sleep apnea and cardiovascular (CV) health. We investigated the current evidence between non-respiratory sleep disorders and CV health. Recent Findings: Current evidence suggests an important association between sleep duration, circadian rhythm, insomnia, disorders of hypersomnolence and CV health. Sleep-related movement disorders exhibit a moderate association with CV health. Further research is needed to explore the effects of each sleep disorder on CV health. Summary: Given the close association between non-respiratory sleep disorders and CV health, it is crucial to recognize and address sleep disorders in patients with a high CV risk.

Mume Fructus reduces interleukin-1 beta-induced cartilage degradation via MAPK downregulation in rat articular chondrocytes.

Osteoarthritis is the most prevalent type of degenerative arthritis. It is characterized by persistent pain, joint dysfunction, and physical disability. Pain relief and inflammation control are prioritised during osteoarthritis treatment Mume Fructus (Omae), a fumigated product of the Prunus mume fruit, is used as a traditional medicine in several Asian countries. However, its therapeutic mechanism of action and effects on osteoarthritis and articular chondrocytes remain unknown. In this study, we analyzed the anti-osteoarthritis and articular regenerative effects of Mume Fructus extract on rat chondrocytes. Mume Fructus treatment reduced the interleukin-1ß-induced expression of matrix metalloproteinase 3, matrix metalloproteinase 13, and a disintegrin and metalloproteinase with thrombospondin type 1 motifs 5. Additionally, it enhanced collagen type II alpha 1 chain and aggrecan accumulation in rat chondrocytes. Furthermore, Mume Fructus treatment regulated the inflammatory cytokine levels, mitogen-activated protein kinase phosphorylation, and nuclear factor-kappa B activation. Overall, our results demonstrated that Mume Fructus inhibits osteoarthritis progression by inhibiting the nuclear factor-kappa B and mitogen-activated protein kinase pathways to reduce the levels of inflammatory cytokines and prevent cartilage degeneration. Therefore, Mume Fructus may be a potential therapeutic option for osteoarthritis.

REM Sleep Behavior Disorder and Its Possible Prodromes in General Population: Prevalence, Polysomnography Findings, and Associated Factors.

BACKGROUND AND OBJECTIVES: To evaluate the prevalence of REM sleep behavior disorder (RBD) and its possible prodromal conditions, isolated dream enactment behavior (DEB) and isolated REM without atonia (RWA), in a general population sample, and the factors associated with diagnosis and symptom frequency. METHODS: From a population-based prospective cohort in Korea, 1,075 participants (age 60.1 ± 7.0 years; range 50-80 years; men 53.7%) completed the RBD screening questionnaire (RBDSQ), a structured telephone interview for the presence and characteristics of repeated DEB, and home polysomnography (PSG). RWA was measured on submentalis EMG, including 30-second epoch-based tonic and phasic activity as well as 3-second mini-epoch-based phasic and any EMG activities. Based on the presence of repeated DEB and any EMG activity of ≥22.3%, we categorized the participants into no RBD, isolated RWA, isolated DEB, and RBD groups. RESULTS: RBD was diagnosed in 20 participants, isolated RWA in 133 participants, and isolated DEB in 48 participants. Sex and DEB frequency-adjusted prevalence of RBD was 1.4% (95% CI 1.0%-1.8%), isolated RWA was 12.5% (95% CI 11.3%-13.6%), and isolated DEB was 3.4% (95% CI 2.7%-4.1%). Total RBDSQ score was higher in the RBD and isolated DEB groups than in the isolated RWA and no RBD group (median 5 [interquartile range (IQR) 4-6] for RBD, median 4 [IQR 3-6] for isolated DEB, median 2 [IQR 1-3] for isolated RWA, and median 2 [IQR 1-4] for no RBD groups, p < 0.001). RBDSQ score of ≥5 had good specificity but poor positive predictive value (PPV) for RBD (specificity 84.1% and PPV 7.7%) and its prodromal conditions (specificity 85.2% and PPV 29.1%). Among the RWA parameters, any EMG activity showed the best association with the RBD and its possible prodromes (area under the curve, 0.917). Three-second mini-epoch-based EMG activity and phasic EMG activity were correlated with the frequency of DEB (standardized Jonckheere-Terpstra statistic [std. J-T static] for trend = 0.488, p < 0.001, and std. J-T static = 3.265, p = 0.001, respectively). DISCUSSION: This study provides prevalence estimates of RBD and its possible prodromal conditions based on a structured telephone interview and RWA measurement on PSG from the general population.

Longitudinal Trends in Sleep and Related Factors Among South Korean Adults From 2009 to 2018.

BACKGROUND AND PURPOSE: Excess or insufficient sleep, irregular sleep-wake patterns, and an extreme early or late chronotypes adversely impact physical and mental health. Changes in sleep characteristics should therefore be tracked, and factors that contribute to poor sleep should be identified. We investigated the changes in sleep patterns among South Korean adults during 2009-2018. METHODS: Using data of a representative sample of South Korean adults from the 2009 (n=2,658, 48.5% males; age=44.5±15.0 years old [mean±standard deviation], age range=19-86 years) and 2018 (n=2,389, 49.1% males; age=47.9±16.3 years, age range=19-92 years) Korean Headache-Sleep Study, we explored changes in sleep timing, sleep duration, chronotype, and social jetlag (SJL). Logistic regression analysis was used to examine the association between average sleep duration and depression. RESULTS: From 2009 to 2018, bedtimes were advanced by 10 and 25 min on workdays and free days, respectively. Meanwhile, wake-up times were advanced by 13 min and delayed by 12 min on workdays and free days, respectively. The average sleep duration significantly decreased from 7.45 h to 7.13 h. The prevalence of short sleep duration (<7 h) increased, whereas that of long sleep duration (≥8 h) decreased. A circadian preference toward eveningness and SJL increased. The prevalence of depression increased from 4.6% to 8.4%, and there were significant reverse J-shaped and U-shaped associations between average sleep duration and depression in 2009 and 2018, respectively. CONCLUSIONS: Changes in sleep patterns and the association between sleep duration and depressive mood were determined from a representative sample of the South Korean adult population. Interventions to modify sleep behaviors might improve public health.

Complex Extract of Polygonatum sibiricum and Nelumbinis semen Improves Menopause Symptoms via Regulation of Estrogen Receptor Beta in an Ovariectomized Rat Model.

Menopause is a hormone-deficiency state that causes facial flushing, vaginal dryness, depression, anxiety, insomnia, obesity, osteoporosis, and cardiovascular disease as ovarian function decreases. Hormone-replacement therapy is mainly used to treat menopause; however, its long-term use is accompanied by side effects such as breast cancer and endometriosis. To identify the effect of a complex extract of Polygonatum sibiricum (PS) and Nelumbinis semen (NS) on improving menopause without side effects, an ovariectomized rat model was established to analyze several menopause symptoms. Compared to single extracts, the complex extract restored vaginal epithelial cell thickness and decreased serotonin concentration by increasing the estrogen receptors ERα (ESR1) and ERß (ESR2), depending on the ratio. Although the complex extract exerted a lower weight-loss effect than the single extracts, improved blood-lipid metabolism was observed after increasing high-density lipoprotein cholesterol levels and decreasing low-density lipoprotein cholesterol and triglyceride levels, and ovariectomy-induced osteoporosis was alleviated by suppressing osteoclast production. Thus, by increasing only ERß expression without regulating ERα expression in the uterus, the complex extract of PS and NS may be a natural treatment for improving menopause symptoms without side effects, such as endometriosis.

The association between social jetlag and depression is independent of sleep debt.

OBJECTIVES: To investigate whether the association between SJLsc (sleep-corrected social jetlag) and depressive mood is significant and independent of sleep debt. METHODS: Participants from the general adult population were interviewed using structured questionnaires on sleep duration, weekday/weekend sleep schedules, and depressive mood (Patient Health Questionnaire-9). Social jetlag (SJL) was measured by SJLsc and standard SJL (SJLs). SJLs was the absolute difference between mid-sleep time on free days (MSF) and workdays (MSW). For SJLsc, both MSF and MSW were adjusted for average sleep duration across the week according to the direction of sleep debt. Sleep debt was defined by sleep extension on free days. The association of SJL with depression was investigated, and covariates included age, sex, sociodemographic factors, insomnia symptoms, sleep duration, and sleep debt. RESULTS: A total of 1982 individuals (1089 men; age 43.1 ± 14.4 years) were analyzed. SJL was present in 24.6% measured by SJLsc and 51.0% by SJLs. SJLsc and SJLs were significantly associated with depressive mood (r = 0.06, P = 0.02; r = 0.06, P = 0.01, respectively), independent of sleep debt. Sleep debt was also associated with depression (r = 0.07, P < 0.01). CONCLUSIONS: By adopting sleep-corrected formula for SJL, this study found that misaligned and insufficient sleep, at levels occurring in routine social life, can negatively affect mood. Minimizing social jetlag and sleep deprivation may promote individual psychological well-being.

Association between older subjective age and poor sleep quality: a population-based study.

OBJECTIVE: To examine the association of subjective age (SA) with sleep quality in an adult population. METHODS: In the Korean Sleep and Headache Study, 2,349 participants (49.2% men; 48.1 ± 16.4 years old) were interviewed face-to-face using structured questionnaires between September and December 2018. SA was assessed by asking participants their perceived age in years and then compared with their chronological age (CA). Participants were assigned to three groups: feeling younger, feeling their age, and feeling older. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Association between SA and sleep quality was analyzed with multiple linear regression controlling for demographics, psychosocial, and sleep characteristics. RESULTS: The group feeling older (n = 404, 17.2%; men, 58.2%; age, 46.5 ± 16.2 years) had worse sleep quality than the groups feeling younger and feeling their age (PSQI score, 4.3 ± 2.7, 3.8 ± 2.4, 3.4 ± 2.1, respectively, p <.001; prevalence of poor sleep quality, 29.0%, 18.4%, 13.5% respectively, p <.001). The association between SA and the PSQI score remained significant after adjusting for confounders (ß = 1.05, 95% confidence interval 0.26, 1.83; p <.001). Stratified analyses by sex and CA showed that the association between SA and the PSQI score was significant only in women and in middle-aged and older group (aged 50-79), suggesting that sex and CA modified the association. CONCLUSION: Age perception was associated with self-reported sleep quality, independent of CA. SA may be a useful marker that complements the conventional assessment of subjective sleep quality.

Quantitative electroencephalographic analysis of delirium tremens development following alcohol-withdrawal seizure based on a small number of male cases.

INTRODUCTION: Seizures and delirium tremens (DTs) are recognized as severe alcohol-withdrawal symptoms. Prolonged admission and serious complications associated with alcohol withdrawal are responsible for increased costs and use of medical and social resources. This study investigated the predictive value of quantitative electroencephalography (QEEG) for developing alcohol-related DTs after alcohol-withdrawal seizure (AWS). METHODS: We compared differences in QEEG in patients after AWS (n = 13). QEEG was performed in the intensive care unit within 48 h of admission, including in age- and sex-matched healthy controls. We also investigated the prognostic value of QEEG for the development of alcohol DTs after AWS in a retrospective, case-control study. The spectral power of each band frequency and the ratio of the theta to alpha band (TAR) in the electroencephalogram were analyzed using iSyncBrain® (iMediSync, Inc., Korea). RESULTS: The beta frequency and the alpha frequency band power were significantly higher and lower, respectively, in patients than in age- and sex-matched healthy controls. In AWS patients with DTs, the relative beta-3 power was lower, particularly in the left frontal area, and the TAR was significantly higher in the central channel than in those without DTs. CONCLUSION: Quantitative EEG showed neuronal excitability and decreased cognitive activities characteristic of AWS associated with alcohol-withdrawal state, and we demonstrated that quantitative EEG might be a helpful tool for detecting patients at a high risk of developing DTs during an alcohol-dependence period.

Polygonatum sibiricum improves menopause symptoms by regulating hormone receptor balance in an ovariectomized mouse model.

Female menopause is a hormone deficiency phenomenon that causes hot flashes, vaginal dryness, depression, nervous tension, insomnia, obesity, and bone loss. There are various hormone replacement therapy (HRT)-based menopausal treatments, but they are accompanied by side effects such as endometrial cancer and hyperplasia. To confirm the menopausal improvement effect of Polygonatum sibiricum (PS), we prepared an ovariectomized animal model, administered 17ß-estradiol (E2) and PS, and analyzed various menopausal symptoms. PS restored vaginal epithelium thickness, by increasing the expression of estrogen receptors ERα (ESR1) and ERß (ESR2), and increased serotonin concentration by reducing serotonin receptor 1 A (5-HT1A) and glucocorticoid receptor (Gr) expression. In addition, PS suppressed obesity by increasing HDL-C and decreasing LDL-C levels and improved the osteoporosis induced by ovariectomy. In particular, by controlling Hand2, Fgf2, and Faf9 expression through PR, the antiproliferative signal was suppressed in uterine epithelium, thereby reducing the risk of side effects of the administration of E2 alone. These results demonstrate that PS alleviates menopausal symptoms without causing endometrial hyperplasia.

Association of Obstructive Sleep Apnea With White Matter Integrity and Cognitive Performance Over a 4-Year Period in Middle to Late Adulthood.

Importance: Obstructive sleep apnea (OSA) is associated with cognitive impairment and brain structural alterations, but longitudinal outcomes are understudied. Objective: To examine the associations of OSA with cognition and white matter (WM) integrity over a 4-year period. Design, Setting, and Participants: This prospective cohort study was conducted in a community-based adult population among participants who had both baseline (2011-2014) and 4-year follow-up (2015-2018) polysomnography, diffusion tensor imaging, and cognitive assessment data. Participants with neurological disorders, anomalous findings on brain magnetic resonance imaging, or inadequate quality of the evaluations were excluded. Data were analyzed from March to November 2021. Exposures: Participants were categorized depending on the presence vs absence of OSA at baseline and follow-up polysomnographic analysis. Main Outcomes and Measures: The main outcomes were proportional changes over a 4-year period in neuropsychological performance and WM integrity. The neuropsychological assessment battery included verbal and visual memory, verbal fluency, Digit Symbol-coding, Trail Making Test-A, and Stroop Test. WM integrity was assessed by fractional anisotropy, axial, and radial diffusivity. To examine interactions with age and sex, participants were subgrouped by age older than 60 years vs 60 years or younger and men vs women. Results: A total of 1998 individuals were assessed for eligibility, and 888 were excluded based on exclusion criteria, leaving 1110 participants (mean [SD] age, 58.0 [6.0] years; 517 [46.6%] men) for analysis, including 458 participants grouped as OSA-free, 72 participants with resolved OSA, 163 participants with incident OSA, and 417 participants with persistent OSA. Incident OSA was associated with altered WM integrity and with concomitant changes in sustained attention compared with participants without OSA (eg, change in Digit Symbol-coding test score, -3.2% [95% CI, -5.2% to -1.2%]). Participants with resolved OSA showed better visual recall at the follow-up (change in Visual Reproduction-immediate recall test, 17.5% [95% CI, 8.9% to 26.1%]; change in Visual Reproduction-delayed recall test, 33.1% [95% CI, 11.3% to 54.9%]), with concordant changes in diffusion parameters at the relevant anatomic areas. In the older group only (age >60 years), persistent OSA was associated with altered WM integrity and cognition (eg, Visual Reproduction-recognition test: ß = -24.2 [95% CI, -40.7 to -7.7]). Sex also was associated with modifying the association of OSA with WM integrity of the left posterior internal capsule, the left genu of corpus callosum, and the right middle cerebellar peduncle only in men and with cognition only in women (eg, Visual Reproduction-immediate recall test: ß = 33.4 [95% CI, 19.1 to 47.7]). Conclusions and Relevance: These findings suggest that dynamic changes in OSA status were significantly associated with WM integrity and cognition, which varied by age and sex. It is possible that adequate interventions for OSA could better preserve brain health in middle to late adulthood.

Deep Learning-Based Assessment of Brain Connectivity Related to Obstructive Sleep Apnea and Daytime Sleepiness.

PURPOSE: Obstructive sleep apnea (OSA) is associated with altered pairwise connections between brain regions, which might explain cognitive impairment and daytime sleepiness. By adopting a deep learning method, we investigated brain connectivity related to the severity of OSA and daytime sleepiness. PATIENTS AND METHODS: A cross-sectional design applied a deep learning model on structural brain networks obtained from 553 subjects (age, 59.2 ± 7.4 years; men, 35.6%). The model performance was evaluated with the Pearson's correlation coefficient (R) and probability of absolute error less than standard deviation (PAE

Neurotherapeutic Potential of Cervus elaphus Sibericus on Axon Regeneration and Growth Cone Reformation after H2O2-Induced Injury in Rat Primary Cortical Neurons.

Cervus elaphus sibericus (CES), commonly known as deer antler, has been used as a medicinal herb because of its various pharmacological activities, including its anti-infective, anti-arthritic, anti-allergic, and anti-oxidative properties. However, the precise mechanisms by which CES functions as a potent anti-oxidative agent remain unknown; particularly, the effects of CES on cortical neurons and its neurobiological mechanism have not been examined. We used primary cortical neurons from the embryonic rat cerebral cortex and hydrogen peroxide to induce oxidative stress and damage in neurons. After post-treatment of CES at three concentrations (10, 50, and 200 µg/mL), the influence of CES on the neurobiological mechanism was assessed by immunocytochemistry, flow cytometry, and real-time PCR. CES effectively prevented neuronal death caused by hydrogen peroxide-induced damage by regulating oxidative signaling. In addition, CES significantly induced the expression of brain-derived neurotrophic factor and neurotrophin nerve growth factor, as well as regeneration-associated genes. We also observed newly processing elongated axons after CES treatment under oxidative conditions. In addition, filopodia tips generally do not form a retraction bulb, called swollen endings. Thus, CES shows therapeutic potential for treating neurological diseases by stimulating neuron repair and regeneration.

Sleep structure and electroencephalographic spectral power of middle-aged or older adults: Normative values by age and sex in the Korean population.

The fine structure of sleep electrocortical activity reflects health and disease. The current study provides normative data for sleep structure and electroencephalography (EEG) spectral power measures derived from overnight polysomnography (PSG) and examines the effect of age and sex among Korean middle-aged and older adults with or without obstructive sleep apnea (OSA). We analysed home PSG data from 1,153 adult participants of an ongoing population-based cohort study, the Korean Genome and Epidemiology Study. Sleep stages were visually scored and spectral power was measured on a single-channel EEG (C4-A1). We computed spectral power for five frequency ranges. The EEG power was reported in relative (%) and log-transformed absolute values (µV2 ). With ageing, the proportion of N1 sleep increased, whereas N3 decreased, which is more noticeable in men than in women. The amount of N3 was relatively low in this cohort. With ageing, relative delta power decreased and alpha and sigma power increased for the whole sleep period, which was more pronounced during REM sleep in non-OSA. For men compared with women, relative theta power was lower during REM and sigma and beta were higher during N1 sleep. The differences of relative powers by age and sex in OSA were comparable to those in non-OSA. In a community-based Korean population, we present normative data of sleep structure and spectral power for middle-aged or older adults of a non-Caucasian ethnicity. The values varied with age and sex and were not influenced by sleep apnea.

Transient Homonymous Superior Quadrantanopsia in Nonketotic Hyperglycemia: A Case Report and Systematic Review.

BACKGROUND AND PURPOSE: Nonketotic hyperglycemia often causes transient visual field defects, but only scattered anecdotes are available in the literature. METHODS: We report a patient with homonymous superior quadrantanopsia due to nonketotic hyperglycemia and provide a systematic literature review of the clinical features of 40 previously reported patients (41 in total, including our case) with homonymous visual field defects in association with nonketotic hyperglycemia. RESULTS: The typical visual field defect was congruous (84.6%), homonymous hemianopsia (87.8%) with macular splitting (61.5%) or sparing (38.5%). It was transient and repetitive in 54.5% of the patients, but it developed as a persistent form in the remainder. Positive visual symptoms such as hallucinations and phosphenes developed in 73.2% of patients. Brain MRI revealed corresponding abnormalities in most patients (84.8%), characterized by a low-intensity white-matter signal or a high-intensity gray-matter signal on T2-weighted or fluid-attenuated inversion recovery images with diffusion restriction or gadolinium enhancement. Most (97.0%) patients recovered completely, with 48.5% treated by glycemic control alone and the remainder also receiving antiepileptic agents. CONCLUSIONS: Nonketotic hyperglycemia should be considered a possible cause of transient visual field defects, especially when it is associated with repetitive positive visual symptoms and typical MRI findings in hyperglycemic patients.

Effects of Aluminum on the Integrity of the Intestinal Epithelium: An in Vitro and in Vivo Study.

BACKGROUND: Aluminum (Al) is the most abundant and ubiquitous metal in the environment. The main route of human exposure to Al is through food and water intake. Although human exposure to Al is common, the influence of Al on the gastrointestinal tract remains poorly understood. OBJECTIVES: We aimed to further understand the toxic effect of Al and to elucidate the underlying cellular mechanisms in the intestinal barrier. METHODS: The human intestinal epithelial cell line HT-29 and C57BL6 mice were exposed to AlCl3 at 0-16 mM (1-24h) and 5-50mg/kg body weight (13 weeks), respectively. In cell culture experiments, intracellular oxidative stress, inflammatory protein and gene expression, and intestinal epithelial permeability were measured. In animal studies, histological examination, gene expression, and myeloperoxidase (MPO) activity assays were conducted. RESULTS: Cellular oxidative stress level (superoxide production) in AlCl3-treated cells (4 mM, 3h) was approximately 38-fold higher than that of the control. Both protein and mRNA expression of tight junction (TJ) components (occludin and claudin-1) in AlCl3-treated cells (1-4 mM, 24h) was significantly lower than that of the control. Transepithelial electrical resistance (TEER) decreased up to 67% in AlCl3-treated cells (2 mM, 24h) compared with that of the control, which decreased approximately 7%. Al activated extracellular signal-regulated kinase 1/2 and nuclear factor-kappa B (NF-κB), resulting in mRNA expression of matrix metalloproteinase-9, myosin light-chain kinase, and inflammatory cytokines [tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and IL-6] in HT-29 cells. Moreover, oral administration of AlCl3 to mice induced pathological alteration, MPO activation, and inflammatory cytokine (TNF-α, IL-1ß, and IL-6) production in the colon. CONCLUSION: Al induced epithelial barrier dysfunction and inflammation via generation of oxidative stress, down-regulation of the TJ proteins, and production of inflammatory cytokines in HT-29 cells. In addition, Al induced toxicity in the colon by increasing the levels of inflammatory cytokines and MPO activity and induced histological damage in a mouse model. Our data suggest that Al may be a potential risk factor for human intestinal diseases. https://doi.org/10.1289/EHP5701.

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells.

Zearalenone (ZEN) is a mycotoxin produced by Fusarium species; however, its mechanisms of action in human livers have not been fully elucidated. Thus, we investigated the toxic mechanisms of ZEN in human liver cells. HepG2 cells were treated with ZEN (0-40 µg/mL) for up to 24 h. A significant decrease in cell viability was observed after treatment with 20 and 40 µg/mL of ZEN, including a significant increase in apoptosis and reactive oxygen species production. ZEN increased GRP78 and CHOP, and eIF2α phosphorylation, indicating ER stress; elevated transcription of the autophagy-associated genes, beclin1 and LC3, and translation of LC3; and increased phase I metabolism by increasing PXR and CYP3A4. The protein expression level of CYP3A4 was higher with ZEN treatment up to 20 µg/mL, but remained at the control level after treatment with 40 µg/mL ZEN. In phase II metabolism, Nrf2 activation and UGT1A expression were increased with ZEN treatment up to 20 µg/mL. Treating cells with an ER stress inhibitor alleviated ZEN-induced cell death and autophagy, and inhibited the expression of phase I/II enzymes. Overall, high ZEN concentrations can modulate the expression of phase I/II enzymes via ER stress and reduced protein levels in human liver cells.

Piperlongumine Induces Cell Cycle Arrest via Reactive Oxygen Species Accumulation and IKKß Suppression in Human Breast Cancer Cells.

Piperlongumine (PL), a natural product derived from long pepper (Piper longum L.), is known to exhibit anticancer effects. However, the effect of PL on cell cycle-regulatory proteins in estrogen receptor (ER)-positive breast cancer cells is unclear. Therefore, we investigated whether PL can modulate the growth of ER-positive breast cancer cell line, MCF-7. We found that PL decreased MCF-7 cell proliferation and migration. Flow cytometric analysis demonstrated that PL induced G2/M phase cell cycle arrest. Moreover, PL significantly modulated the mRNA levels of cyclins B1 and D1, cyclin-dependent kinases 1, 4, and 6, and proliferating cell nuclear antigen. PL induced intracellular reactive oxygen species (hydrogen peroxide) accumulation and glutathione depletion. PL-mediated inhibition of IKKß expression decreased nuclear translocation of NF-κB p65. Furthermore, PL significantly increased p21 mRNA levels. In conclusion, our data suggest that PL exerts anticancer effects in ER-positive breast cancer cells by inhibiting cell proliferation and migration via ROS accumulation and IKKß suppression.

Effect of Fermented Medicinal Plants as Dietary Additives on Food Preference and Fecal Microbial Quality in Dogs.

This research determined the antioxidant activities of medicinal plants fermented by Enterococcus faecium and their subsequent applications as dog food additives. Turmeric (5%, w/v), glasswort (2.5%, w/v), Ganghwa mugwort (2.5%, w/v), and their mixture (5%, w/v) were fermented by autochthonous E. faecium (1%, v/v) for 72 h. Bacterial cell counts and pH were monitored during fermentation. Total polyphenol content (TPC), total flavonoid content (TFC), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, and intracellular superoxide scavenging activity in bovine mammary alveolar epithelial (MAC-T) cells were measured with the fermented and non-fermented samples. Only the antioxidant capacity of the mixture was increased after fermentation. However, intracellular superoxide level in MAC-T cells was significantly reduced after treatment with fermented plant samples (p < 0.001) as compared with that in non-fermented plants. Fermented plants were then sprayed at 1% (v/w) onto dog foods. TPC, TFC, ABTS radical scavenging activity, and DPPH radical scavenging activity of dog foods were significantly enhanced after the addition of fermented plants. Food preference testing was conducted using a two-pan method-control diet vs. four treatment diets-for 4 days for each additive diet, a total 16 days in 9 beagles. Feces were collected to enumerate bacterial counts. Preferences for glasswort and Ganghwa mugwort were higher than those of the control (p < 0.05). Furthermore, fecal microbiota enumeration displayed a higher number of beneficial microorganisms in treated groups. These results suggest that fermented plants with enhanced antioxidant abilities might be useful as potential additives for dog foods.

Prevalence and Characteristics of Restless Legs Syndrome in Korean Adults: A Study in Two Independent Samples of the General Population.

BACKGROUND: Restless legs syndrome (RLS) is a common sleep disorder, although it has a low prevalence in Asian populations. However, the reported RLS prevalence in -Korean adults is mostly 4.5-12.1%, which is higher than that reported in other Asian populations. This study aimed to diagnose RLS and exclude mimicking conditions in 2 independent samples of Korean adults, and to compare its prevalence to that from previous studies performed in Asian countries. METHODS: Study populations included a (1) nationwide stratified random sample (n = 2,824; age 19-79 years) and (2) community-based cohort (n = 2,685; age 47-79 years). We applied the Cambridge-Hopkins diagnostic questionnaire to diagnose RLS and differentiate it from RLS mimics. Sleep-related symptoms, mood, and medical conditions were compared between the RLS and non-RLS groups. Prior studies of the RLS prevalence in Asia were systematically reviewed and compared to our findings. RESULTS: The adjusted RLS prevalence was 0.4 and 1.3% in populations 1 and 2, respectively. In both populations, subjects with RLS had more depression. The prevalence of RLS mimics was 5.1 and 2.6%, in populations 1 and 2, respectively. The RLS prevalence in Asia was higher when RLS was defined by the presence of essential clinical features and lower when a differential diagnosis was additionally implemented. CONCLUSIONS: The RLS prevalence in Korean adults considering RLS mimics is comparable to that in adults from other Asian countries (< 2%). The reported RLS prevalence varies depending on the diagnostic method employed.